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Mesenchymal stromal cells inhibit proliferation of virus-specific CD8(+) T cells

25227910

Projects: WP5: Translational Application for the Characterization and ex vivo Expa...

Leukemia
17th Sep 2014

G. Malcherek, N. Jin, A. G. Huckelhoven, J. Mani, L. Wang, U. Gern, A. Diehlmann, P. Wuchter, A. Schmitt, B. Chen, A. D. Ho, M. Schmitt

Abstract:

Mesenchymal stromal cells (MSCs) possess broad immunomodulatory capacities that are currently investigated for potential clinical application in treating autoimmune disorders. Third-party MSCs suppress alloantigen-induced proliferation of peripheral blood mononuclear cells providing the rationale for clinical use in graft-versus-host disease (GvHD). We confirmed that MSCs strongly inhibited proliferation of CD8(+) T cells in a mixed lymphocyte reaction. However, MSCs also suppressed proliferation of T cells specifically recognizing cytomegalovirus (CMV) and influenza virus. Inhibition was dose dependent, but independent of the culture medium. MSCs inhibited proliferation of specific CD8(+) T cells and the release of IFN-gamma by specific CD8(+) T cells for immunodominant HLA-A2- and HLA-B7- restricted antigen epitopes derived from CMV phosphoprotein 65 and influenza matrix protein. This is in contrast to a recently reported scenario where MSCs exert differential effects on alloantigen and virus-specific T cells potentially having an impact on surveillance and prophylaxis of patients treated by MSCs.

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Marcel Schilling

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